Mutation screening for prenatal and presymptomatic diagnosis: cystic fibrosis and haemochromatosis

Abstract

Hereditary haemochromatosis (HH) and cystic fibrosis (CF) are the most common autosomal recessively inherited disorders in Caucasian populations. In its typical form, CF manifests during the first years of life, while the mean age of onset of organ damage is 54 years in HH. Both disorders can be diagnosed presymptomatically utilising biochemical and/or genetic testing. Since approximately 90% of mid-European HH patients are homozygous for only one specific mutation (C282Y) in the candidate gene for HH, genetic testing is simple and sensitive in HH. In CF, molecular testing is currently hampered by the large number (more than 800) of mutations in the CF transmembrane conductance regulator gene. Several studies have been initiated to investigate the potential benefits and the best time and mode of presymptomatic testing for HH and CF.

Conclusion Mutation analysis is widely recommended for presymptomatic diagnosis of cystic fibrosis and hereditary haemochromatosis because of the presumed benefit, although several medical, ethical, social and technical questions warrant further investigations. Prenatal mutation testing is commonly performed for cystic fibrosis but not for hereditary haemochromatosis. Informed consent of tested individuals and the availability of genetic counselling is a prerequisite for any mutation screening approach in either disease.